Few methods permit the hydrogenation of alkenes to a thermodynamically favored configuration when steric effects dictate the alternative trajectory of hydrogen delivery. Dissolving metal reduction achieves this control, but with extremely low functional group tolerance. Here we demonstrate a catalytic hydrogenation of alkenes that affords the thermodynamic alkane products with remarkably broad functional group compatibility and rapid reaction rates at standard temperature and pressure.

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays. Characterization of the library in terms of physicochemical properties, structural diversity, and similarity to compounds in publicly available libraries indicates that the Canvass library contains many structural elements in common with approved drugs. The assay data generated were analyzed using a variety of quality control metrics, and the resultant assay profiles were explored using statistical methods, such as clustering and compound promiscuity analyses. Individual compounds were then sorted by structural class and activity profiles. Differential behavior based on these classifications, as well as noteworthy activities, are outlined herein. One such highlight is the activity of (−)-2(S)-cathafoline, which was found to stabilize calcium levels in the endoplasmic reticulum. The workflow described here illustrates a pilot effort to broadly survey the biological potential of natural products by utilizing the power of automation and high-throughput screening.

A nitrosopurine-ene reaction easily assembles the asmarine pharmacophore and transmits remote stereochemistry to the diazepine-purine hetereocycle. This reaction generates potent cytotoxins that exceed the potency of asmarine A (1.2 μM IC 50 ) and supersede the metabolites as useful leads for biological discovery. Keywordsalkaloids; terpenoids; nitroso; purine; ene reaction Asmarines A and B (1&2, Figure 1) were identified in 1998 by Kashman and co-workers as the bioactive constituents of a Red Sea sponge (Raspailia sp.) extract, exhibiting cytotoxicity against several cancer cell lines with a minimum EC 50 of 1.2 μM and 120 nM, respectively. [1] The asmarines are unique among alkaloids by virtue of the embedded Nhydroxypurine diazepine (primary pharmacophore) [2] connected by an ethyl bridge to a

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